Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway

Abstract Andrographolide derivatives or analogs exhibit potent anti-inflammatory effects in several disease models through NF-κB activity. In this study, we synthesized different andrographolide derivatives and investigated their effects on the toll-like receptor (TLR)-induced production of pro-infl...

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Autores principales:	Xin Nie, Shao-Ru Chen, Kun Wang, Yuran Peng, Yi-Tao Wang, Decai Wang, Ying Wang, Guo-Chun Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/124559caff544f75908efbc0ce914048
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spelling	oai:doaj.org-article:124559caff544f75908efbc0ce9140482021-12-02T12:31:52ZAttenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway10.1038/s41598-017-04673-x2045-2322https://doaj.org/article/124559caff544f75908efbc0ce9140482017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04673-xhttps://doaj.org/toc/2045-2322Abstract Andrographolide derivatives or analogs exhibit potent anti-inflammatory effects in several disease models through NF-κB activity. In this study, we synthesized different andrographolide derivatives and investigated their effects on the toll-like receptor (TLR)-induced production of pro-inflammatory cytokines. Among these compounds, 3b, 5a, and 5b inhibited both TNF-α/NF-κB and TLR4/NF-κB signaling pathways. Treatment with compounds 3b, 5a, and 5b and their structural analogs, 3a and 6b, suppressed the expression of pro-inflammatory cytokines upon the activation of TLR3 and TLR4 ligands. Compounds 3b and 5a, but not 3a, 5b, or 6b, inhibited the nuclear translocation of the NF-κB p65 subunit. Treatment with compounds 3b, 5a, 3a, 5b, and 6b attenuated the phosphorylation of p65 and IκBα. Compounds 6b suppressed the expression of the NF-κB p65 subunit. However, these compounds, except for 5b, did not affect the TLR9-induced NF-κB-independent production of the pro-inflammatory cytokines, TNF-α, and IFN-β. Compound 3b potentially protected mice from LPS-induced acute pulmonary inflammation through the inhibition of p65 phosphorylation and the decrease of serum pro-inflammatory cytokines and chemokine. Our study revealed a functional structure–activity relationship between andrographolide derivatives and innate immunity. We identified compound 3b as a potent immune suppressive agent with the potential to protect acute pulmonary infection.Xin NieShao-Ru ChenKun WangYuran PengYi-Tao WangDecai WangYing WangGuo-Chun ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xin Nie Shao-Ru Chen Kun Wang Yuran Peng Yi-Tao Wang Decai Wang Ying Wang Guo-Chun Zhou Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway
description	Abstract Andrographolide derivatives or analogs exhibit potent anti-inflammatory effects in several disease models through NF-κB activity. In this study, we synthesized different andrographolide derivatives and investigated their effects on the toll-like receptor (TLR)-induced production of pro-inflammatory cytokines. Among these compounds, 3b, 5a, and 5b inhibited both TNF-α/NF-κB and TLR4/NF-κB signaling pathways. Treatment with compounds 3b, 5a, and 5b and their structural analogs, 3a and 6b, suppressed the expression of pro-inflammatory cytokines upon the activation of TLR3 and TLR4 ligands. Compounds 3b and 5a, but not 3a, 5b, or 6b, inhibited the nuclear translocation of the NF-κB p65 subunit. Treatment with compounds 3b, 5a, 3a, 5b, and 6b attenuated the phosphorylation of p65 and IκBα. Compounds 6b suppressed the expression of the NF-κB p65 subunit. However, these compounds, except for 5b, did not affect the TLR9-induced NF-κB-independent production of the pro-inflammatory cytokines, TNF-α, and IFN-β. Compound 3b potentially protected mice from LPS-induced acute pulmonary inflammation through the inhibition of p65 phosphorylation and the decrease of serum pro-inflammatory cytokines and chemokine. Our study revealed a functional structure–activity relationship between andrographolide derivatives and innate immunity. We identified compound 3b as a potent immune suppressive agent with the potential to protect acute pulmonary infection.
format	article
author	Xin Nie Shao-Ru Chen Kun Wang Yuran Peng Yi-Tao Wang Decai Wang Ying Wang Guo-Chun Zhou
author_facet	Xin Nie Shao-Ru Chen Kun Wang Yuran Peng Yi-Tao Wang Decai Wang Ying Wang Guo-Chun Zhou
author_sort	Xin Nie
title	Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway
title_short	Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway
title_full	Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway
title_fullStr	Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway
title_full_unstemmed	Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway
title_sort	attenuation of innate immunity by andrographolide derivatives through nf-κb signaling pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/124559caff544f75908efbc0ce914048
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_version_	1718394202107150336

Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway

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